This proposal seeks funds to purchase an ABI QSTAR ELITE quadrupole/time- of-flight (QqTOF) hybrid mass spectrometer for confident elucidation of post-translational modifications of proteins in complex biological mixtures and analysis of small molecules. The requested instrumentation is essential for the emerging research needs of eleven NIH-sponsored major users at the Weill Medical College of Cornell University and a cadre of more than twenty minor users. The QqTOF will be made available to investigators by inclusion in the Medical College's Mass Spectrometry CORE, a facility that opened in 1997 with committed institutional support for staff and operations. The MS CORE facility provides the sole source of mass spectrometric analysis to researchers at the Weill Medical College and associated hospitals. The modest resources for MS-based analyses is currently outstripped by demand Fundamental to the regulation of a protein's function are its moment-to-moment changes in covalent postranslational modifications (PTMs). Thus, it is not only important to identify and quantify a cell's protein contingent, but also the covalent modifications that are key to biological control. To address this need, a variety of powerful and high- throughput technologies have recently emerged, relying on MS for specification and quantification of protein PTMs. These new and evolving MS approaches have been successfully exploited in numerous studies to rigorously identify dozens of PTMs on hundreds of proteins in complex biological milieu. Here we propose to make such instrumentation for analysis of protein PTMs available to biomedical scientists at the Weill Medical College. Access of the major user group to the requested technology will be utilized for the detection and relative quantitation of protein phosphorylation, methylation, nitrosylation, nitration and ubiquitination -- this will significantly advance their NIH-supported research in areas extending from cell-cell communication, stem cell biology, oogenesis, brain function, neuronal signaling and differentiation. Use of the QqTOF will extend to analysis of small biological molecules, taking advantage of the instrument's ability for accurate mass determination and quantification. Award of the QqTOF MS system will markedly expand the capabilities of the MS CORE facility at Weill Cornell and benefit the research programs of dozens of NIH-supported biomedical investigators that it serves annually. [unreadable] [unreadable] [unreadable]